Registration Dossier
Registration Dossier
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EC number: 272-249-5 | CAS number: 68784-47-4
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Read across valid as the substnace tested is also titanate complex with glycol and alkylamine, degrading in water to similar degradation products.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell transformation assay
- Species / strain / cell type:
- mammalian cell line, other: Chinese hamster ovary cells
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 50 ... 5000 µg/ml
Concentration range in the main test (without metabolic activation): 50 ... 5000 µg/ml - Vehicle / solvent:
- DMSO (dimethylsulfoxide)
- Details on test system and experimental conditions:
- Fixation time:
24 hours. In one experiment, cells were treated continuously
without S9 for 46 hours and harvested at 48 hours. - Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 µg/ml
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- Observations:
No toxicity was observed, although precipitation above 250
micrograms per plate without S9 made evaluation impossible.
No increase in the frequency of aberrant metaphase was
observed. - Conclusions:
- The test substance was negative with and without metabolic activiation. There was no evidence that the substance induced chromosomal aberrations in the presence or absence of S9 mix.
The visible precipitation at higher concentrations may be a result of titanium dioxide forming during abiotic degradation - Executive summary:
The target substance was negative in genetic toxicity, read-across from study of structural analogue.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell transformation assay
- Species / strain / cell type:
- mammalian cell line, other: Chinese hamster ovary cells
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 50 ... 5000 µg/ml
Concentration range in the main test (without metabolic activation): 50 ... 5000 µg/ml - Vehicle / solvent:
- DMSO (dimethylsulfoxide)
- Details on test system and experimental conditions:
- Fixation time:
24 hours. In one experiment, cells were treated continuously
without S9 for 46 hours and harvested at 48 hours. - Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 5000 µg/ml
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- Observations:
No toxicity was observed, although precipitation above 250
micrograms per plate without S9 made evaluation impossible.
No increase in the frequency of aberrant metaphase was
observed. - Conclusions:
- The test substance was negative with and without metabolic activiation. There was no evidence that the substance induced chromosomal aberrations in the presence or absence of S9 mix.
The visible precipitation at higher concentrations may be a result of titanium dioxide forming during abiotic degradation - Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell transformation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor-induced rat liver S9 mix.
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 78.1 ... 1875 μg/ml
Concentration range in the main test (without metabolic activation): 78.1 ... 1875 - Vehicle / solvent:
- ethanol
- Details on test system and experimental conditions:
- Exposure period (with metabolic activation): 3 hours
Exposure period (without metabolic activation): 24 hours
Expression time:
2 days
Selection time:
10-14 days - Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ( 2500 µg/ml)
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- No increase in the mutation frequency was seen under any treatment conditions used.
- Conclusions:
- The test substance was negative with and without metabolic activation. The test material did not induce any toxicologically significant increases at the TK +/- locus in L5178Y cells
A precipitate was observed, possibly from titanium dioxide formed during hydrolysis - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver S9
- Test concentrations with justification for top dose:
- Concentration range in the main test (with metabolic activation): 33 ... 10000 µg/plate
Concentration range in the main test (without metabolic activation): 33 ... 10000 µg/plate - Vehicle / solvent:
- Sterile, ultra-pure water
- Key result
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 10000 µg/plate
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- Observations:
No toxicity was observed
Precipitation was observed at concentrations > 333 mg/plate- this is considered to be titanium dioxide and it is likely that precipitation at lower level was not possible to observe.
An increase in revertants was observed only in strain TA
1535 with metabolic activation at 333 and 1000 micrograms
per plate. Two repeat experiments were unable to confirm
this observation. - Conclusions:
- It was concluded that the substnace is not mutagenic in Salmonella typhimurium.
E Coli strains were also tested and shown to be negative
Referenceopen allclose all
A concomitant reverse mutation test in Escherichia coli strain WP2 uvrA was also negative. Precipitation of the substance was observed at 333 and 10,000 micrograms per plate with S9 only.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Extensive testing and reviews have been conducted on titanium dioxide, triethanolamine and propylene glycol, demonstrating that there is no mutagenic potential.
An IARC monograph on triethanolamine suggests that there is no evidence for mutagenicity, and this is cited in the IUCLID file. WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 77
Some Industrial Chemicalshttp://monographs.iarc.fr/ENG/Monographs/vol77/volume77.pdf
Titanium dioxide has been extensively investigated, especially in nano-form for use in cosmetics and several review documents suggest low risk. One citation is in Drug Chemistry and Toxicology, 2011 July 34(3):277-84.Cytotoxicity and genotoxicity of titanium dioxide nanoparticles in UVA-irradiated normal peripheral blood lymphocytes: Kang, Lee et al.
Propylene glycol has also been extensively evaluated and review documents suggest low risk of mutagenic potential. A review by the US EPA (Prevention Pesticides and Toxic Substances, EPA-739-R-06-002, September 2006) http://www.epa.gov/oppsrrd1/REDs/propylene_glycol_red.pdf
Propylene glycol and dipropylene glycol were tested for mutagenic or genotoxic potential and found to be negative in a battery of studies: a bacterial gene mutation assay using Salmonella typhimurium, and in vitro Chinese hamster ovary (CHO) mutation assay, an in vitro Chinese hamster ovary (CHO) chromosomal aberration assay and an in vitro sister chromatid exchange assay.
Propan-2-ol is reported in a review by the EU Scientific Committee on Health and Environmental Risks conclude low toxic risk (25th plenary on 9 September 2008), but suggests that data is limited with regard to in-vitro mutagenicity evaluation.
Justification for classification or non-classification
Negative results in all testing performed and from review of metabolites
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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